A Functionalized 20‐Residue Peptaibol Derivative for Nucleic Acid Delivery

Based on the membrane‐modifying peptaibol trichocellin‐A‐I ( 1 ) from Trichoderma viride , we designed a vehicle for the cellular delivery of antisense oligodeoxynucleotides by attaching a (Lys) 10 stretch to the C‐terminus of 1 . The resulting transporter peptide 2 , prepared by solid‐phase synthesis using Fmoc protocol in combination with amino acid fluorides, was found to be mainly α ‐helical in solution, in contrast to its precursors 1 and 3 . The uptake of the complex formed between carrier 2 and a fluorescence‐tagged oligonucleotide, i.e. , 4 , was studied at different charge ratios by confocal laser‐scanning microscopy, using two different eukaryotic cell lines: mouse embryonal fibroblast (NIH3T3) and human lung carcinoma (A549) cells. Peptide 2 readily translocated 4 into the cytoplasms of NIH3T3 cells. However, the peptide/oligonucleotide complex was accumulated around the plasma membrane of the A549 cells.